Size of the subcutaneous tumor (glioblastoma U87 cells). Spectroscopic photoacoustic imaging provides blood oxygen saturation map of the tumor at the same cross-section. The oxygen saturation maps are pseudo colored on a black (0 ) to red (100 ) scale. Immunofluorescence image at the same cross section of the tumor is obtained post-euthanasia. The vasculature is stained in green while red stain shows the hypoxic regions in the tumor. Hypoxic conditions are caused in PDT either due to consumption during the process or via vascular coagulation post-PDT. Here we observe that deeper tumor regions had no hypoxia stain (indicated by yellow arrows) or reduction in oxygen saturation indicating insufficient light dose reaching these deeper tissues. Incorporating therapy monitoring techniques to identify non-responsive or untreated areas is highly important and critical to prevent subsequent regrowth of these regions by designing PD-148515 molecular weight appropriate therapy. Figure adapted from Mallidi et al. [47]http://www.thno.orgTheranostics 2016, Vol. 6, Issuetumor treated with BPD based PDT are shown in Fig. 4. Sufficient light dose (illumination at 690 nm) did not reach the bottom of the tumor (yellow arrows), thereby causing little to no damage to this region of the tumor. Given the heterogeneity in the tumor microenvironment, it is critical to incorporate imaging technologies that can sufficiently sample disease regions for markers such as vasculature, oxygen saturation, necrosis, blood flow changes etc. to assess potentially non-responsive areas and predict treatment response. Recently, techniques that directly monitor the singlet oxygen generated during PDT have also been employed to predict treatment response [45]. An extensive review of direct and indirect treatment response strategies in PDT have been provided elsewhere [15, 48] and are considered beyond the scope of this review. Overall, to achieve efficient therapeutic benefit from PDT, specifically also for deep GW 4064 site tissue PDT, it is of paramount importance to monitor microenvironmental conditions and provide the “right or optimal” light dose (fluence rate and fluence) and illumination regime according to the photosensitizer concentration at the treatment site [49].from enzymatic activity [51]. Phillip et al. were the first to report the use of chemiluminescent probes in the late 1980’s [52]. They demonstrated in vivo that a peroxyoxalate chemiluminescent solution could activate the HpD Photofrin II, concluding that chemically activated luminescence could be a promising option for PDT in deep tissues. More recently, Huang et al. demonstrated that luminol activated by ferrous sulphate could excite the meso-tetraphenylporphyrin (TPP) PS inducing an effective decrease in the viability of Caco2 cells [53]. Yuan et al. confirmed these results by demonstrating a complete spectroscopic validation of the energy transfer between the oxidized luminol and the OPV, a cationic oligo (p-phenylene vinylene) PS [54]. Generation of ROS and cell death was confirmed in vitro in this chemi-luminescent based PDT study. The authors performed an in vivo study that demonstrated the combination of oxidized luminol and OPV could slow tumor growth with minimal systemic toxicity in HeLa tumor-bearing mice. Despite their promise, chemiluminescent probes usually exhibit systemic toxicity that may limit their widespread adoption. A few years after the introduction of chemiluminescence based PDT, Carpenter et al. reported the first use of b.Size of the subcutaneous tumor (glioblastoma U87 cells). Spectroscopic photoacoustic imaging provides blood oxygen saturation map of the tumor at the same cross-section. The oxygen saturation maps are pseudo colored on a black (0 ) to red (100 ) scale. Immunofluorescence image at the same cross section of the tumor is obtained post-euthanasia. The vasculature is stained in green while red stain shows the hypoxic regions in the tumor. Hypoxic conditions are caused in PDT either due to consumption during the process or via vascular coagulation post-PDT. Here we observe that deeper tumor regions had no hypoxia stain (indicated by yellow arrows) or reduction in oxygen saturation indicating insufficient light dose reaching these deeper tissues. Incorporating therapy monitoring techniques to identify non-responsive or untreated areas is highly important and critical to prevent subsequent regrowth of these regions by designing appropriate therapy. Figure adapted from Mallidi et al. [47]http://www.thno.orgTheranostics 2016, Vol. 6, Issuetumor treated with BPD based PDT are shown in Fig. 4. Sufficient light dose (illumination at 690 nm) did not reach the bottom of the tumor (yellow arrows), thereby causing little to no damage to this region of the tumor. Given the heterogeneity in the tumor microenvironment, it is critical to incorporate imaging technologies that can sufficiently sample disease regions for markers such as vasculature, oxygen saturation, necrosis, blood flow changes etc. to assess potentially non-responsive areas and predict treatment response. Recently, techniques that directly monitor the singlet oxygen generated during PDT have also been employed to predict treatment response [45]. An extensive review of direct and indirect treatment response strategies in PDT have been provided elsewhere [15, 48] and are considered beyond the scope of this review. Overall, to achieve efficient therapeutic benefit from PDT, specifically also for deep tissue PDT, it is of paramount importance to monitor microenvironmental conditions and provide the “right or optimal” light dose (fluence rate and fluence) and illumination regime according to the photosensitizer concentration at the treatment site [49].from enzymatic activity [51]. Phillip et al. were the first to report the use of chemiluminescent probes in the late 1980’s [52]. They demonstrated in vivo that a peroxyoxalate chemiluminescent solution could activate the HpD Photofrin II, concluding that chemically activated luminescence could be a promising option for PDT in deep tissues. More recently, Huang et al. demonstrated that luminol activated by ferrous sulphate could excite the meso-tetraphenylporphyrin (TPP) PS inducing an effective decrease in the viability of Caco2 cells [53]. Yuan et al. confirmed these results by demonstrating a complete spectroscopic validation of the energy transfer between the oxidized luminol and the OPV, a cationic oligo (p-phenylene vinylene) PS [54]. Generation of ROS and cell death was confirmed in vitro in this chemi-luminescent based PDT study. The authors performed an in vivo study that demonstrated the combination of oxidized luminol and OPV could slow tumor growth with minimal systemic toxicity in HeLa tumor-bearing mice. Despite their promise, chemiluminescent probes usually exhibit systemic toxicity that may limit their widespread adoption. A few years after the introduction of chemiluminescence based PDT, Carpenter et al. reported the first use of b.